Maintenance of the cell shape is a metabolically dependent process involving the cell surface and the submembranous actin and tubulin-rich cytoskeleton. The rapid and reversible cell contraction and rounding produced by certain pharmacological agents will be used as a model to study mechanisms which determine cell adhesion and motility and may be altered in transformed or neoplastic cells. These studies are also relevant to cytotoxicity phenomena mediated by lymphocytes and macrophages. We propose to : 1) examine cell surface and cytoskeleton changes during exposure to agents such as local anesthetics, cytochalasins or chelators. Cell shape and surface changes will be analysed by time-lapse cinemicrography in conjunction with transmission and scanning electron microscopy. Immunocytochemistry for actin and tubulin will also be used to study the cytoskeleton. We will determine if cell rounding is a patterned response elicited by all agents or if there are specific features of the rounding induced by certain agents; 2) compare the patterns of response of normal and transformed cells to selected rounding agents in order to determine altered mechanisms regulating cell shape; 3) investigate the modulating effect which other agents such as lectins, metabolic inhibitors, D2O or cyclic nucleotides have on the rounding response. These experiments are designed to elucidate the cellular mechanisms and requirements underlying the response; 4) determine whether micromanipulative application of pharmacological agents to limited areas of the cell surface will result in localized changes in cell shape, such as localized spreading, rounding or zeiosis. If a segmental response similar to that which occurs in phagocytosis is observed, a model for the study of translational movement may be developed.